This invention relates to a drug for the improvement of the circulation in the optic nerve head, particularly a drug for the treatment of normal tension glaucoma, which comprises as an active ingredient Lomerizine or a pharmaceutically acceptable acid addition salt thereof.
Glaucoma is one of the main causes of blindness and is defined as xe2x80x9can eye disease characterized by an increase in intraocular pressure and a temporary or permanent optic nerve dysfunction due to the increase in intraocular pressure.xe2x80x9d Although this definition may be adopted to glaucoma with high intraocular pressure such as the angle-closure glaucoma or secondary glaucoma, it is not adoptable to the normal tension glaucoma without association of the increase in intraocular pressure.
Recently, attention has been given to the normal tension glaucoma which is set by optic peripheral circulation disorder such as optic nerve head circulation disorder, while the intraocular tension is within the normal range. Accordingly, various studies have been done on the syndromes thereof and for finding a method for the treatment of the disease.
On the other hand, it is known that calcium antagonists are effective for ocular circulation. The calcium antagonists can block electric potential-dependent calcium channel in the excitatory cells such as smooth muscle and cardiac muscle, inhibit flow of Ca ion into cells which induce relaxation of smooth muscle and inhibit the contraction of cardiac muscle, and thereby have widely been used for the treatment of angina pectoris and hypertension. It is also known that the actions of the calcium antagonists onto the ocular circulation are different depending on the kinds of calcium antagonists. For example, with respect to the action on the optic nerve head, Nicardipine shows week activity but Nilvadipine shows an activity of increasing blood flow in the optic nerve head (cf. xe2x80x9cNichi-Gan Kaishixe2x80x9d (Journal of Japanese Ophthalmology Society), Vol. 100, No. 12, p. 923, 1996).
Lomerizine having the following chemical formula (I) or a pharmaceutically acceptable acid addition salt thereof is a calcium antagonist having a benzylpiperazine nucleus as disclosed in JP-A-60-222472, and the dihydrochloride compound (Lomerizine hydrochloride) is now being developed as a drug for the treatment of migraine in the code name of KB 2796. 
JP-A(Kohyo)-7-508030 discloses a topical ophthalmic composition for the treatment of glaucoma, which comprises a combination of a calcium antagonist and a compound having an activity of decreasing or controlling the intraocular pressure, wherein many kinds of known calcium antanogists including KB 2796 are disclosed.
It is disclosed in the above Japanese patent publication that the known calcium antagonists used in the topical ophthalmic composition for the treatment of glaucoma are xe2x80x9cpreferably those having decrease of ocular perfusion pressure and having tendency of decrease of ocular blood flow in case of lowering not so much the systemic blood pressurexe2x80x9d (cf. the description thereof, page 4, upper right column, end linexe2x80x94lower left column, line 2).
However, to the contrary, Lomerizine or a pharmaceutically acceptable acid addition salt thereof does neither lower the systemic blood pressure nor decrease the ocular perfusion pressure, but can increase the ocular blood flow, as is mentioned hereinafter.
Besides, the above patent publication discloses merely the name KB 2796, but does never teach or even suggest the activity of Lomerizine or a pharmaceutically acceptable acid addition salt thereof onto the optic nerve head circulation.
It has been strongly desired to use a drug having no systemic action such as hypotensive activity for the clinical treatment of the normal tension glaucoma.
An object of this invention is to provide a novel drug for the improvement of the optic nerve head circulation, which has no systemic action such as hypotensive activity and is useful for the treatment of the normal tension is glaucoma.
The present inventors have intensively studied and found that among the many kinds of calcium antagonists, Lomerizine or a pharmaceutically acceptable acid addition salt thereof shows little hypotensive activity, that is, has weak peripheral vasodilating activity and does not increase the peripheral blood flow, but can surprisingly increase the blood flow in the ocular periphery (the optic nerve head), and then have completed this invention.